The heterogeneity of asymmetric tau distribution is associated with an early age at onset and poor prognosis in Alzheimer’s disease

Background This study aimed to investigate whether an asymmetric tau distribution on PET images could be associated with clinical characteristics and prognosis in prodromal and/or clinical Alzheimer’s disease (AD). Method The testing cohort consisted of 60 patients with mild cognitive impairment due to AD and AD dementia from the Alzheimer’s Disease Neuroimaging Initiative – who underwent tau PET imaging with the first‐generation tau tracer [18F]flortaucipir. The validation cohort consisted of an independent sample of 67 patients enrolled from the Shanghai Memory Study who underwent PET tau imaging with the second‐generation tau tracer [18F]APN‐1607. Based on the absolute global tau interhemispheric differences, each cohort was divided into two groups (asymmetric versus symmetric tau distribution). The two groups were cross‐sectionally compared in terms of demographic and cognitive characteristics, as well as pathological burden. The cognitive trajectories of cognitive decline were analyzed longitudinally. Result Fourteen patients (23.3%) in the testing cohort and 26 (38.8%) in the validation cohort showed an asymmetric tau distribution. In both cohorts, cross‐sectional results consistently revealed that an asymmetric tau distribution was associated with an earlier age at disease onset and more severe tau and amyloid burden (Fig 1). In longitudinal analyses, patients with an asymmetric tau distribution were characterized by a steeper cognitive decline (Fig 2). Conclusion An asymmetric tau distribution on PET images was consistently associated with an earlier age at onset and more severe pathological features of AD in two independent cohorts. Additionally, this imaging biomarker was longitudinally associated with a more rapid trajectory of cognitive decline.